The <Guide to Leukemia-Lymphoma Cell Lines> summarizes the salient characteristics of 560 cell lines: precursor B (85), mature B (155), plasma cell leukemia/myeloma (66), immature T (55), mature T (21), natural killer (10), Hodgkin lymphoma (10), anaplastic large cell lymphoma (16), myelocytic (62), monocytic (33) and erythrocytic-megakaryocytic cell lines (45). Along with other improvements, the advent of continuous human leukemia-lymphoma (LL including myeloma) cell lines as a rich resource of abundant, accessible and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. The first LL cell lines, Burkitt lymphoma-derived lines, were established in 1963. Since then more than 1500 cell lines have been described, some 500 of them in detail. The major advantages of continuous cell lines is the unlimited supply and worldwide availability of identical cell material and the infinite viable storability in liquid nitrogen. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro with preservation of most cellular features, and specific genetic alterations characteristic of their tumor of origin. Recent transcriptional profiling studies have confirmed that LL cell lines stably retain the aberrant profiles typical of their tumors of origin. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines should be discerned from Epstein-Barr virus-immortalized normal cells. The efficiency of cell line establishment is rather low and the deliberate establishment of new LL cell lines remains by and large an unpredictable process. Difficulties in establishing continuous cell lines may be caused by the inappropriate selection of nutrients and growth factors. Clearly, a generally suitable microenvironment for hematopoietic cells, either malignant or normal, cannot yet be defined. The characterization and publication of new LL cell lines should provide important and informative core data, attesting to their scientific significance. Large percentages of LL cell lines are contaminated with mycoplasma (about 20%) or are cross-contaminated with other cell lines (14% in our DNA fingerprinting analysis on 622 samples covering 560 LL cell lines). Solutions to these problems are sensitive detection, effective elimination and rigorous prevention of mycoplasma infection and proper, regular authentication of cell lines. The underlying cause appears to be negligent cell culture practice. The willingness of investigators to make their LL cell lines available to others is all too often limited. There is a need in the scientific community for clean and authenticated high quality LL cell lines to which every scientist has access. These are offered by public cell line banks like the DSMZ which holds 169 LL cell lines which all have undergone a strict quality, identity and characterization program (immunoprofile, karyotype, DNA fingerprint, virus/mycoplasma check). An example of the practical utility of LL cell lines are the recent advances in studies of classical and molecular cytogenetics which in large part were made possible by cell lines. We propose a list of the most useful, robust and publicly available reference cell lines which may be used for a variety of experimental purposes. The <Guide to Leukemia-Lymphoma Cell Lines> is available on CD; inquire at <firstname.lastname@example.org>.